The conference goal is to increase our understanding of the effects of ionizing radiation on cells, such that improved therapeutic strategies can be developed to increase tumor cell killing and to reduce the effects on normal cells. The biological basis of the response to DNA damage has become increasingly well understood in the last 15 years. However, relatively little research has focused on tumor cell versus normal cell differences, where there is a clear opportunity to capitalize on specific tumor cell deficiencies in the DNA damage response to optimize the therapeutic effects of ionizing radiation. Known differences in the DNA damage response in tumors have been found in relation to chromatin organization, cell cycle checkpoint responses, checkpoint adaptation, management of the stalled replication fork, repair by homologous recombination and its relative role in double-strand break repair, the effect of hypoxia on DNA repair and epigenetic regulatory mechanisms. These topics form the basis of this latest cutting-edge GRC conference in Radiation Oncology. The unique feature of this conference is the focus on tumor related differences in the DNA damage response and the implications of these basic science observations in the treatment of human cancer by radiation therapy. Each discussion leader will be given clear instructions on developing new translational initiatives as a result of the scientific presentations. The invited speakers will be encouraged to develop a section of their talk in discussing potential therapeutic applications. The consequence of this research conference should improve current novel strategies for improving the therapeutic ratio in radiation oncology. Improving the effectiveness of radiation therapy, which is used in the treatment of 50% of all human cancers, will have a major impact on current approaches to treatment. [unreadable] [unreadable] [unreadable] [unreadable]